This bioengineering research grant is responsive to PA-07-279 (reissue of PA-06-419). It is a collaboration between the University of Massachusetts Medical School and the Utah Center for Advanced Imaging Research at University of Utah. Superposition of breast structures in screen-film and digital mammography may result in missed cancers due to 'masking'effect, or may mimic the presence of a lesion resulting in additional imaging or biopsy. Dedicated breast Computed Tomographic (CT) imaging of the breast can overcome this superposition problem, and provide much improved contrast, thus improving lesion detectability. Further, breast CT can be performed at low radiation dose (equivalent to mammography) with no or minimal physical compression of the breast, alleviating patient discomfort. It can provide for 3-D lesion morphology, which could serve as a diagnostic indicator, and for better quantitative assessment of breast glandular content, a likely risk factor for breast cancer. This work is focused on design and optimization of a dedicated breast CT system. Specifically, the research plan is to address known challenges in breast CT, such as maximizing the inclusion of breast tissue within scan field, determining appropriate source-detector trajectory with consideration for data completeness and reconstruction complexity, and developing noise suppression schemes to improve microcalcification visibility. The research plan includes determining optimal patient position for maximizing breast tissue inclusion, implementation of several image acquisition trajectories and appropriate reconstruction algorithms, comprehensive mathematical simulation and optimization of critical system and reconstruction parameters. Complete characterization of the improvement achieved on a bench-top system will be performed through observer-independent physical metrics and through surgical mastectomy specimen-based observer studies. The results from this study will provide for an ergonomic design and optimized image acquisition and reconstruction technique that can be readily translated to a clinical imaging system. A well-designed dedicated breast CT system can serve as a platform technology for screening and diagnostic imaging, implant imaging, 3-D presurgical planning, monitoring preoperative treatment, and guidance in minimally invasive surgery. We believe our approach will have a major impact on the detection and management of breast cancer. PUBLIC HEALTH RELEVANCE: Volumetric 3-D imaging with a dedicated breast CT system has the potential to be an effective tool to overcome the tissue superposition problem in mammography which results in missed cancers and unnecessary recall of the patient for additional imaging, and for monitoring the effectiveness of therapeutic treatments. However, there are known challenges such as maximizing breast tissue inclusion during the scan, visualization of microcalcifications due to image noise and loss of contrast, and cone- beam artifacts. In this research, we propose to develop methods to overcome these challenges and demonstrate the improved image quality obtained with such methods.